Temgicoluril

Temgicoluril
Clinical data
Trade namesAdaptol, Mebicar
Other namesAdaptol; Mebicar; Mebicarum; Mebikar; Tetramethylglycoluril; 1,3,4,6-Tetramethylglycoluril
ATC code
Legal status
Legal status
  • US: Unscheduled; not FDA approved
Pharmacokinetic data
MetabolismGastrointestinal tract: 77–80%
Elimination half-life3 hours[1]
ExcretionUrine: 55–70%
Identifiers
  • 1,3,4,6-Tetramethyltetrahydroimidazo[4,5-d]imidazole-2,5(1H,3H)-dione
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC8H14N4O2
Molar mass198.226 g·mol−1
3D model (JSmol)
  • CN1C2C(N(C1=O)C)N(C(=O)N2C)C
  • InChI=1S/C8H14N4O2/c1-9-5-6(11(3)7(9)13)12(4)8(14)10(5)2/h5-6H,1-4H3
  • Key:XIUUSFJTJXFNGH-UHFFFAOYSA-N

Temgicoluril (INNTooltip International Nonproprietary Name),[2] also known as tetramethylglycoluril and sold under the brand names Adaptol and Mebicar, is an anxiolytic medication produced by Latvian pharmaceutical company Olainfarm and sold in Latvia and Russia.[3]

The chemical structure of temgicoluril is somewhat similar to uric acid and it doesn't interact with acids, alkali, oxidants and reducing agents. It seems to affect all major neurotransmitter systems.[4]

Temgicoluril has an effect on the structure of limbic–reticular activity, particularly on hypothalamus emotional zone, as well as on all several basic neuromediator systems – γ aminobutyric acid (GABA), choline, serotonin, and adrenergic activity. It decreases brain norepinephrine levels and increases brain serotonin levels without modulating dopaminergic systems or cholinergic systems.[5]

Temgicoluril purportedly has anti-anxiety (anxiolytic) properties.[5][6][7][8][9] It is also used to aid smoking cessation.[3] In addition, temgicoluril may be useful in the treatment of ADHD symptoms.[10] In contrast with typical anxiolytic medications such as benzodiazepines, temgicoluril is non-habit forming, non-sedating, and does not impair motor function.[6][3]

It can be prepared by condensation of N,N-dimethylurea with glyoxal. One publication described such a procedure. They combined N,N-dimethylurea and glyoxal with a catalytic amount of phosphoric acid anhydride in an aqueous solution at room temperature and after sufficient time temgicoluril was conveniently isolated by filtration. The filtrate can be re-used by adding more dimethylurea and glyoxal (no additional catalyst is needed) and obtaining respectable yields, although this requires a longer reaction time.[11]

As of 2021, temgicoluril has not been evaluated outside of Latvia and Russia.

Medical uses

Temgicoluril is used in Latvia and Russia, as a pharmaceutical drug to treat anxiety and to prevent or reduce anxiety, unrest, fear, internal emotional tension and irritability, reduce neuroses and neurotic disorders, heartburns of non-coronary heart disease origin. These effects are not accompanied with relaxation of muscle tone and impaired coordination of movement, suppression of mental and physical activity, so the drug can be used without interruption of work or school.

Temgicoluril does not have a direct effect on sleep, however, it enhances the effectiveness of sleep medicines and normalizes the course of disturbed sleep. Temgicoluril alleviates or eliminates the manifestations of nicotine dependence that occur after smoking cessation. Although temgicoluril does not cause mood swings or euphoria, habituation, nor addiction, withdrawal syndrome has been observed.[contradictory]

Side effects

Possible and rare side effects may include dizziness, hypotension, indigestion, allergic reactions (itchy skin) after high doses, hypothermia, fatigue. And lowered blood pressure and/or body temperature decreased by 1 to 1.5 °C. Blood pressure and body temperature return to normal after completion of treatment.[12]

See also

References

  1. ^ US 20110070305, Schwarz J, Weisspapir M, "Sustained release pharmaceutical composition containing mebicar", published 2011-03-24, assigned to Alpharx Inc. 
  2. ^ "International Nonproprietary Names for Pharmaceutical Substances (INN)" (PDF). WHO Drug Information. 34 (3). 2020.
  3. ^ a b c "Adaptol product summary". JSC Olainfarm. Latvia. Archived from the original on 2013-10-13. Retrieved 2013-05-29.
  4. ^ "Clinical Overview ADAPTOL" (PDF). JSC Olainfarm. Latvia. Archived (PDF) from the original on 8 September 2021.
  5. ^ a b Val'dman AV, Zaikonnikova IV, Kozlovskaia MM, Zimakova IE (May 1980). "[Characteristics of the psychotropic spectrum of action of mebicar]". Biulleten' Eksperimental'noi Biologii I Meditsiny. 89 (5): 568–570. PMID 6104993.
  6. ^ a b Val'dman AV, Zaikonnikova IV, Kozlovskaya MM, Zimakova IE (1980). "A study of the spectrum of psychotropic action of mebicar". Bulletin of Experimental Biology and Medicine. 89 (5): 621–624. doi:10.1007/BF00835799. S2CID 11343572.
  7. ^ Mkrtchian VR, Kozhokova LZ (2012). "[Adaptol--verges of possible]". Likars'ka Sprava (5): 125–133. PMID 23534281.
  8. ^ Chutko LS, Rozhkova AV, Sidorenko VA, Surushkina SI, Tursunova KB (2012). "[Generalized anxiety disorder: psychosomatic aspects and treatment approaches]". Zhurnal Nevrologii I Psikhiatrii Imeni S.S. Korsakova. 112 (1): 40–44. PMID 22678674.
  9. ^ Chutko LS, Surushkina SI, Nikishena IS, Iakovenko EA, Anisimova TI, Kuzovenkova MP (2010). "[Asthenic disorders in children]". Zhurnal Nevrologii I Psikhiatrii Imeni S.S. Korsakova. 110 (11 Pt 1): 26–29. PMID 21183919.
  10. ^ Chutko LS, Surushkina SI, Nikishena IS, Iakovenko EA, Anisimova TI, Sergeev AV (2009). "[Adaptol in the treatment of ADHD]". Zhurnal Nevrologii I Psikhiatrii Imeni S.S. Korsakova. 109 (8): 45–48. PMID 19738569.
  11. ^ Micheletti G, Delpivo C, Baccolini G (2013-06-01). "A green synthesis of glycoluril derivatives in aqueous solution with recycle of the waste". Green Chemistry Letters and Reviews. 6 (2): 135–139. Bibcode:2013GCLR....6..135M. doi:10.1080/17518253.2012.718803. ISSN 1751-8253. S2CID 96318579.
  12. ^ "Adaptol (Mebicarum) - Summary of product characteristics". State Agency of Medicines of Latvia (in Latvian). Archived from the original on 7 August 2021.